Chronic pain in children and young people John M. Goddard Sheffield Children’s Hospital, Western Bank, Sheffield, UK Correspondence to John M. Goddard, MBBS, MRCP, FRCA, FFPMRCA, Consultant in Paediatric Anaesthesia and Pain Medicine, Sheffield Children’s Hospital, Western Bank, Sheffield S10 2TH, UK Tel: +44 114 2717522; fax: +44 1142717183; e-mail: [email protected] Current Opinion in Supportive and Palliative Care 2011, 5:158–163

Purpose of review In response to a considerable volume of clinical research into chronic pain in children and young people, recent systematic reviews now provide an evidence base for management. Clinicians should be aware of this evidence and areas in which evidence is lacking. Recent findings There is a strong evidence base for psychological interventions in several conditions; computerized delivery with therapist support shows promise. Multidisciplinary services are required for a small cohort of patients. The role and effects of parents in their child’s pain is becoming clearer; effective interventions for parents are being developed. The evidence for effective pharmacotherapy is poor, apart from the acute management of headache. Summary Clinicians need to be aware of the therapeutic effect of the psychosocial approach to the management of chronic pain in children and young people. Further research is required into the pharmacological and physical aspects of management, which remain important. Keywords abdominal, chronic disease, headache, musculoskeletal, pain Curr Opin Support Palliat Care 5:158–163 ß 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins 1751-4258

Introduction In this review, chronic pain in children and young people (CAYP) includes recurrent pains such as migraine and recurrent abdominal pain, and persistent pains such as chronic musculoskeletal pain and complex regional pain syndrome. Chronic pain in CAYP is usually considered to be present after a period of 3 months. Epidemiological studies consistently demonstrate that chronic pain in CAYP is prevalent. The point prevalence of chronic and recurrent pain in children and adolescents was identified as at least 15% in a review in 1991 [1]. A large study in Dutch schoolchildren, aged 0–18 years, revealed that a quarter of the respondents reported chronic pain. Girls reported more pain than boys, with peak prevalence at 14 years of age [2]. In a study in Canadian children aged 9–13 years, 57% reported experiencing at least one recurrent pain and 6% were identified as having had or currently having chronic pain. In keeping with studies from other countries, the common problems were headaches, recurrent abdominal pain and musculoskeletal pain [3]. A more recent study of Spanish schoolchildren reported that 5% had moderate or severe chronic pain problems [4]. The management of chronic pain in CAYP depends upon the initial presentation. In the absence of indications of 1751-4258 ß 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins

serious pathology, most families receive reassurance and simple analgesics. In an increasingly investigative environment, specialist referral and screening investigations are often undertaken. Thereafter, if symptoms do not settle, further investigations and referrals tend to occur. Management includes pharmacotherapy, physiotherapy and, if available, psychological therapies. An increasingly large cohort progresses to require multidisciplinary services. High-quality research into the treatment and management of CAYP with chronic pain is predominantly focussed on psychological therapies. There are very few studies concerned with pharmacotherapy or physical therapies. This review will not cover the use of disease modifying drugs for specific conditions.

Methodology ‘New publications on pediatric pain’, a contemporary service available on the Pain in Childhood Special Interest Group of the International Association for the Study of Pain website http://newpubs.childpain.org/, was screened for the period July 2009 to December 2010. A Medline search was also undertaken for the period 2009 to 2010. Selected publications are presented in this review. DOI:10.1097/SPC.0b013e328345832d

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Chronic pain in children and young people Goddard 159

Psychological therapies Psychological therapies are widely utilized in the management of chronic pain in CAYP and their role is clearly justified by available evidence. An updated meta-analytic review of randomized controlled trials of psychological therapies for management of chronic pain in children and adolescents has recently been published [5]. This review includes 25 trials and identifies a large positive effect of psychological intervention on pain reduction at immediate post-treatment and follow-up in youths (6–18 years) with headache, abdominal pain and fibromyalgia. Cognitive behavioural therapy (CBT), relaxation therapy and biofeedback all produced significant and positive effects on pain reduction. Published studies do not allow any comparison of the relative efficacy of different interventions. The review also looked at disability and emotional functioning as outcome measures, but found only small and nonsignificant effects. This work is reported in more detail as a Cochrane review [6]. Compared with previous reviews, the authors note an increase in the quality of recent studies and are confident that the recently published recommendations for outcome domains and measures in paediatric pain trials will increase consistency for future reviews [7].

Key points  Chronic pain in children and young people is prevalent; an increasingly investigative approach in medicine can make management difficult.  Diagnosis and information are highly valued by families; parents, understandably, find parenting a child with chronic pain very stressful.  There is a strong evidence base for the effectiveness of psychological therapies; computerized cognitive behavioural therapy for patients and therapist interventions for parents both show promise.  Multidisciplinary services are required for children and young people severely disabled by chronic pain.  Further research is required, particularly in the fields of pharmacotherapy and physical therapy. and a major weakness was noncompliance with questionnaire return, although compliance with the interventions was good. Computerized delivery of psychological interventions for pain shows promise in CAYP. It remains to be seen how cost-effective this will be as therapist contact appears to remain important.

Multidisciplinary pain services A systematic review confirms these CAYP have fewer friends and are subject to more peer victimization than healthy peers [8]. A critical review suggests effects on cognitive function also [9]. Acceptance of pain is increasingly being recognized as important in limiting disability [10], and a randomized controlled trial reports encouraging results from an acceptance-based intervention in adolescents [11]. Cognitive behavioural therapy is traditionally delivered by a therapist; recently, computerized packages have been developed and evaluated. A review and metaanalysis of computerized CBT (cCBT) for the treatment of pain in children and adolescents has been published [12]. Four studies met the inclusion criteria, all of which indicated beneficial results of using cCBT. Patients with headache, abdominal pain and musculoskeletal pain were involved in packages lasting 4–8 weeks, all of which had weekly sessions. Importantly, I think, all participants had access to a therapist, mostly by weekly phone calls. A further randomized controlled trial has now been published [13] which compared three internet delivered interventions in CAYP with headache. Posttreatment responder rate (50% reduction in headache frequency) was significantly better with cCBT (63%) than relaxation (32%) or education (19%). However, at 6-month follow-up, all interventions had a responder rate of around 60%. This study involved many questionnaires

Many CAYP with chronic pain do not access healthcare services and many are managed by their general practitioners. A proportion of CAYP with chronic pain are managed by their general or specialist paediatrician, clinical psychologist or physiotherapist; a very small proportion develops a complex presentation with severe disability (severe pain, significantly reduced physical function, minimal school attendance and social isolation). For these CAYP with severe disability clinical experience and reports from several countries have supported the need for multidisciplinary services [14,15]. A recent German study reports improvements in pain intensity, pain-related disability, school absence and pain-related coping at 3 months following a 3-week inpatient multimodal treatment; improvement was maintained at 12 months. Response to treatment was similar in children (7–10 years) and adolescents (11–18 years) [16]. Multidisciplinary pain services are expensive to provide and consequently commissioning organizations can be reluctant to fund services. However, the economic costs of chronic pain in adolescence are also high; in 2005 a preliminary study estimated the annual cost of illness to be £3840 million in the UK [17]. The case of need seems clear, but costs of illness are spread across many societal areas and healthcare remains reluctant to fund multidisciplinary services for children with chronic pain.

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160 Pain: nonmalignant disease

Parents The research focus in psychology for effective interventions for CAYP with chronic pain appears to be shifting. Initial focus was on the child or young person, this focus moved on to the family and now attention is turning explicitly to the parents. This topic was recently reviewed [18]. Living with, and caring for, a child with chronic pain is stressful and challenging. First, the review looks at the literature on this topic and second examines research on the effect that parental functioning has on children’s adjustment to chronic pain. The review then explores parental adjustments to other chronic medical conditions and finally makes suggestions for future research on parenting the child with chronic pain. A recent qualitative study [19] confirms that mothers feel helpless, acknowledge that being there as a ‘good parent’ is not always helpful and lament the loss of their ‘normal child’. Evidence for catastrophizing and reinforcement of noncoping skills in the child is discussed. This article is recommended to better understand the many dilemmas facing the parents of a child with chronic pain. These issues are reflected in expectations that parents have from referral to a pain clinic [20]. A desire for information about the causes of their child’s pain and treatment options feature highly, along with information about the effects of pain on both body and mood and effective coping strategies for the child. Parents also highly rate the pain team ‘being there’ for them. Two recent studies affirm parental needs for, and satisfaction with, a biopsychosocial approach. Parents attending a multidisciplinary paediatric abdominal pain clinic reported significantly greater receptivity to beginning prescribed treatments and higher levels of overall satisfaction with the evaluation process, when compared with attendance at a traditional gastroenterology clinic in the same institution [21]. Prescriptions of medications were comparable in both clinics. A laboratory study of mothers viewing video vignettes regarding abdominal pain examined the effects of diagnosis, physician orientation and maternal anxiety [22]. Not surprisingly, anxious mothers receiving diagnoses of functional rather than organic abdominal pain, delivered by a physician with a biomedical compared with a biopsychosocial orientation, were more likely to define this as a catastrophe and be dissatisfied with the physician. Several studies report associations between symptoms in children and their parents; it is not at all clear whether these associations are genetic, either disease-related or psychological, or nongenetic. Frequency of headaches in children is positively influenced by the frequency of headaches in the mother [23] and the parents of children with functional gastrointestinal disorders (FGID) showed a significantly higher prevalence of FGID compared with

the parents of children without FGID [24]. A large population-based prospective study in Norway reports that maternal depression at childrens’ age 18 months and a maternal history of psychological distress (anxiety and depression) at childrens’ age 12 years were both predictive of recurrent abdominal pain in adolescence [25]. Research is beginning to show the clinical utility of CBT for parents of children with chronic pain. A randomized controlled trial comparing CBT – modifying responses to illness and wellness behaviours, and cognitive restructuring of dysfunctional beliefs regarding pain and function – and education regarding gastrointestinal anatomy and physiology and nutritional advice, has shown CBT for parents to be effective in reducing symptom levels in children with FGID [26].

Recurrent abdominal pain A systematic review of prognostic factors for persistence of chronic abdominal pain in children identified eight studies that met the review criteria [27]. Parental gastrointestinal problems were identified as moderate evidence of a risk factor for persistence of chronic abdominal pain in children. There was moderate and strong evidence, respectively, that severity of abdominal pain and female sex had no predictive value. Evidence was assessed to be weak, conflicting or insufficient for 14 other prognostic factors including psychological factors in the child. Obesity was not assessed in this review; a prospective cohort study of 116 children with FGID identified obesity as a highly significant prognostic factor for continuing symptoms at 1 year [28]. Nonetheless, many studies continue to report associations between psychological factors in the child and frequency and severity of symptoms. The relationship between parent symptom talk and child complaints has been demonstrated to be greater in children with high catastrophizing [29]. In the same study, children with high threat appraisals had fewer complaints associated with nonsymptom talk. Children with FGID usually undergo many investigations. A retrospective study in the USA reports that investigations are common, costs are substantial, and yield is minimal [30]. Abdominal ultrasound and computed tomography scans were of no clinical value. In contrast, 10% of endoscopies showed abnormal findings. A prospective study of endoscopy in chronic abdominal pain reports that management was changed in 66% of children based on endoscopic or histological findings [31]. Change included reassurance (37%), proton pump inhibitor trial (24%), antispasmodic medication trial (9%) and food allergy testing (9%). It would seem that blood tests to exclude organic bowel disease and endoscopy,

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Chronic pain in children and young people Goddard 161

particularly to allow reassurance, are appropriate in the management of FGID. Other investigations are unlikely to be helpful if not specifically indicated. A Cochrane review concluded there is a lack of highquality evidence on the effectiveness of dietary interventions – fibre supplements, lactose-free diets or lactobacillus supplementation – for recurrent abdominal pain [32]. Nonetheless studies continue to suggest that small intestinal bacterial overgrowth is associated with abdominal pain and that probiotics may be beneficial in symptom management [33]. There are even suggestions that trials of antibiotics are warranted [34]. Many gastroenterologists continue to use these treatments in selected patients.

Headache The management of paediatric migraine has been reviewed recently [35]. Ibuprofen in adequate dose (7.5–10 mg/kg) is effective if given early in acute attacks; triptans are also effective. Medications used for prevention include amitriptyline, propranolol, pizotifen and antiepileptics. A Dutch systematic review of the treatment of tension type headache concludes that nonsteroidal anti-inflammatory drugs (NSAIDs) are effective for short-term pain relief; ibuprofen being associated with fewest side effects [36]. Paracetamol was more effective than placebo, but less so than NSAIDs. There was insufficient evidence to support or refute the effectiveness of preventive medication. Many studies have looked at relationships between headache and psychopathology in children. Another systematic review concludes that children with migraine do not exhibit more psychological dysfunctioning, but there were 26 outcome measures in only seven included trials [37]. Strong evidence of internalizing behaviour is assessed as being a consequence of the disease rather than primary psychological dysfunction.

Musculoskeletal pain A review of chronic musculoskeletal pain in children, focussing particularly on children with significant disability, concludes there is little evidence for or against the effectiveness of pharmacotherapy, but strong evidence for early targeted physical and psychological interventions [38]. A recent randomized trial comparing an 8-week exercise programme with no intervention, for children with low back pain, reports better clinical outcomes – intensity of pain and prevalence of pain at 6 months – in the exercise group. Results were, however, not statistically significant [39]. Like pharmacotherapy,

physical therapy is embedded in the management of CAYP with chronic pain, but trials meeting modern evidence-based criteria are difficult to perform: for physical therapy difficulties are correct control groups and meaningful outcomes. A longitudinal study of children with juvenile idiopathic arthritis identifies that children with high pain and low disease activity have persistently negative health beliefs [40], once again suggesting this area is one for potential therapeutic intervention.

Neuropathic pain Very little data exist on managing neuropathic pain in children; the subject has been usefully reviewed recently [41]. Complex regional pain syndrome (CRPS) is not uncommon in children and in severe cases produces some of the most challenging patients that present to pain clinics. Physical therapy alone was reported to be highly effective many years ago [42]: many clinicians, however, find a significant proportion of children are unable to participate fully, due to pain, and require a multidisciplinary approach. Movement disorders are increasingly recognized in CRPS and can be very difficult to manage [43]. Multicentre trials for the management of CRPS in children are needed.

Pharmacotherapy A multicentre, randomized, placebo-controlled trial of amitriptyline reported no difference between active drug and placebo in children aged 8–17 years with painpredominant FGID [44]. Recruited from six tertiary pediatric gastroenterology centres in the USA, 83 children with irritable bowel syndrome, functional dyspepsia and functional abdominal pain completed the study. Amitriptyline (10 mg/day, weight 35 kg) or placebo was given for 4 weeks. Two primary outcomes were assessed: approximately 60% of children in both arms reported feeling better; pain relief was reported to be good or excellent in 45% of children receiving placebo and 50% treated with amitriptyline. Anxiety, a secondary outcome, was significantly improved with amitriptyline compared to placebo. Three children withdrew because of minor side effects (two amitriptyline, one placebo). The authors conclude that the efficacy and safety profile of amitriptyline, combined with the inability to use placebo as a drug in practice may justify amitriptyline treatment; this view is one with which I agree. Unfortunately, this study was terminated early, after 4 years, having only recruited 90 of a planned 120 patients: a demonstration of the difficulties in conducting randomized controlled drug trials in children. The only other drug study reported recently is an openlabel safety study of oral almotriptan for the acute treatment of migraine in adolescents [45].

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162 Pain: nonmalignant disease

The lack of marketing authorizations for many drugs used in paediatric practice results in frequent off-license prescribing. This problem is receiving worldwide attention. Within the European Union, new legislation, the ‘Paediatric Regulation’, was introduced in 2007 to govern the development and authorization of medicines for children and requires pharmaceutical companies to consider the needs of the paediatric population during medicine development. Analgesia in children is identified as an area of high therapeutic need, both for new products and existing off-patent medicines. Unfortunately, a recent investigation identifies that the number of approved analgesic studies is disappointingly small [46]. Of 17 submissions to the Paediatric Committee of the European Medicines Agency between September 2007 and March 2010, three were withdrawn, eight were granted a full waiver from paediatric development, and one resulted in a negative opinion. Fifteen clinical trials were approved involving five different products.

Conclusion There is a strong evidence base for psychological interventions in the management of chronic pain in CAYP. An understanding of the distress experienced by parents and the therapeutic effect of a psychosocial approach is critical. Multidisciplinary services are needed for CAYP severely disabled by chronic pain. Further research is required into the pharmacological and physical aspects of management, which remain important.

Acknowledgement Sheffield Children’s NHS Foundation Trust.

References and recommended reading Papers of particular interest, published within the annual period of review, have been highlighted as:  of special interest  of outstanding interest Additional references related to this topic can also be found in the Current World Literature section in this issue (pp. 182–183). 1

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Palermo TM, Eccleston C, Lewandowski AS, et al. Randomized controlled trials of psychological therapies for management of chronic pain in children and adolescents: an updated meta-analytic review. Pain 2010; 148:387– 397. Meta-analysis highlighting the strong evidence base for psychological therapies in the management of chronic pain in CAYP. Updated review providing evidence for the effectiveness of psychological therapies in CAYP with recurrent abdominal pain and fibromyalgia, as well as headache.

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9 

10 McCraken LM, Gauntlett-Gilbert J, Eccleston C. Acceptance of pain in  adolescents with chronic pain: validation of an adapted assessment instrument and preliminary correlation analyses. Eur J Pain 2010; 14:316–320. Validation of an assessment instrument for acceptance of pain in adolescents and confirmation that difficulties with acceptance are associated with more distress and disability. 11 Wicksell RK, Melin L, Lekander M, Olsson GL. Evaluating the effectiveness of  exposure and acceptance strategies to improve functioning and quality of life in longstanding pediatric pain – a randomized controlled trial. Pain 2009; 141:248–257. First study to show the clinical utility of an acceptance-based CBT programme for CAYP with chronic pain. 12 Vellemann S, Stallard P, Richardson T. A review and meta-analysis of  computerised cognitive behaviour therapy for the treatment of pain in children and adolescents. Child Care Health Dev 2010; 36:465–472. Systematic review confirming the acceptability and effectiveness of cCBT for CAYP with chronic pain. Potentially, a very cost-effective intervention. 13 Trautmann E, Kroner-Herwig B. A randomized controlled trial of Internetbased self-help training for recurrent headache in childhood and adolescence. Behav Res Ther 2010; 48:28–37. 14 Eccleston C, Malleson PN, Clinch J, et al. Chronic pain in adolescents: evaluation of a programme of interdisciplinary cognitive behaviour therapy. Arch Dis Child 2003; 88:881–885. 15 De Blecourt ACE, Schiphorst Preuper HR, Van Der Schans CP, et al. Preliminary evaluation of a multidisciplinary pain management programme for children and adolescents with chronic musculoskeletal pain. Dis Rehab 2008; 30:13–20. 16 Hechler T, Blankenburg M, Dobe M, et al. Effectiveness of a multimodal  inpatient treatment for pediatric chronic pain: a comparison between children and adolescents. Eur J Pain 2010; 14:97e1–979e. Further confirmation of the effectiveness of multidisciplinary programmes for CAYP severely affected by chronic pain. First study to report evidence in younger children as well as adolescents. 17 Sleed M, Eccleston C, Beecham J, et al. The economic impact of chronic pain in adolescence: methodological considerations and a preliminary costs-ofillness study. Pain 2005; 119:183–190. 18 Palermo TM, Eccleston C. Parents of children and adolescents with chronic  pain. Pain 2009; 146:15–17. Review of the evidence for understanding the significant stress and anxiety experienced by parents of CAYP with chronic pain. Suggestions for further research, particularly for interventions targeted specifically at parents. 19 Maciver D, Jones D, Nicol M. Parents’ experiences of caring for a child with  chronic pain. Qual Health Res 2010; 20:1272–1282. Qualitative study giving a poignant account of the stresses experienced by the parents of CAYP with chronic pain. 20 Reid K, Lander J, Scott S, Dick B. What do the parents of children who have  chronic pain expect from their first visit to a pediatric chronic pain clinic? Pain Res Manage 2010; 15:158–162. Small study revealing what parents, rather than clinicians, want from a paediatric pain clinic. 21 Schurman JV, Friesen CA. Integrative treatment approaches: family satisfac tion with a multidisciplinary paediatric abdominal pain clinic. Int J Integr Care 2010; 10:e51. Provides evidence that families value the psychosocial aspects provided by a multidisciplinary paediatric pain clinic. 22 Williams SE, Smith CA, Bruehl SP, et al. Medical evaluation of children with  chronic abdominal pain: impact of diagnosis, physician practice orientation, and maternal trait anxiety on mothers’ responses to the evaluation. Pain 2009; 146:283–292. Evidence that psychosocial awareness is important when communicating with the parents of CAYP with chronic pain. 23 Arruda MA, Guidetti V, Galli F, et al. Frequency of headaches in children is  influenced by headache status in mother. Headache 2010; 50:973–980. Familial factors are relevant when considering headaches in children.

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Chronic pain in children and young people Goddard 163 24 Buonavolonta` R, Coccorullo P, Turco R, et al. Familial aggregation in children  affected by functional gastrointestinal disorders. J Pediatr Gastroenterol Nutr 2010; 50:500–505. Familial factors are also important when considering FGID in children. 25 Helgeland H, Sandvik L, Mathiesen KS, Kristensen H. Childhood predictors of  recurrent abdominal pain in adolescence: a 13-year population-based prospective study. J Psychosom Res 2010; 68:359–367. This study suggests that maternal psychopathology is relevant in the cause of recurrent abdominal pain in adolescents. 26 Levy RL, Langer SL, Walker LS, et al. Cognitive-behavioral therapy for children  with functional abdominal pain and their parents decreases pain and other symptoms. Am J Gastroenterol 2010; 105:946–956. First study to specifically identify CBT for parents as helpful in alleviating symptoms in the child. Very likely to stimulate development of future CBT interventions for parents of CAYP with chronic pain. 27 Gieteling MJ, Bierma-Zeinstra SM, van Leeuwen Y, et al. Prognostic factors  for persistence of chronic abdominal pain in children: a systematic review. J Pediatr Gastroenterol Nutr 2010 [Epub]. Systematic review identifying a lack of evidence for many currently held theories of prognostic factors for FGID. Familial factors, however, have a strong evidence base. 28 Bonilla S, Wang D, Saps M. Obesity predicts persistence of pain in children  with functional gastrointestinal disorders. Int J Obes (Lond) 2010 [Epub]. Suggests a new and novel prognostic factor for the persistence of FGID in children. 29 Williams SE, Blount RL, Walker LS. Children’s pain threat appraisal and  catastrophizing moderate the impact of parental verbal behaviour on children’s symptom complaints. J Pediatr Psychol 2010 [Epub]. This study identifies a specific aspect of parental behaviour that is amenable to psychological intervention with parents. 30 Dhroove G, Chogie A, Saps M. A million-dollar work-up for abdominal pain: is  it worth it? J Pediatr Gastroenterol Nutr 2010; 51:579–583. Identifies the utility of investigations for FGID in CAYP. Potential to prevent unnecessary and costly investigations.

35 Hershey AD. Current approaches to the diagnosis and treatment of paediatric  migraine. Lancet Neurol 2010; 9:190–204. Recent authoritative review on the management of paediatric migraine. A common disorder with good evidence for its acute treatment, which if widely used would significantly benefit many CAYP. 36 Verhagen AP, Damen L, Berger MY, et al. Treatment of tension type head ache: paracetamol and NSAIDs work: a systematic review. Ned Tijdschr Geneeskd 2010; 154:A1924. Unfortunately, a systematic review in Dutch, but the English abstract provides helpful evidence for the management of tension type headaches in CAYP. 37 Bruijn J, Locher H, Passchier J, et al. Psychopathology in children and  adolescents with migraine in clinical studies: a systematic review. Pediatrics 2010; 126:323–332. Systematic review concluding that it is unhelpful to seek psychopathology in CAYP with migraine. 38 Clinch J, Eccleston C. Chronic musculoskeletal pain in children: assessment  and management. Rheumatology 2009; 48:466–474. Recent review of chronic musculoskeletal pain from a rheumatology perspective. 39 Fanucchi GL, Stewart A, Jordaan R, Becker P. Exercise reduces the intensity  and prevalence of low back pain in 12–13 year old children: a randomised trial. Aust J Physiother 2009; 55:97–104. Physical therapy is widely used in chronic musculoskeletal pain in CAYP, but evidence is not extensive. 40 Thastum M, Herlin T. Pain-specific beliefs and pain experience in children with  juvenile idiopathic arthritis: a longitudinal study. J Rheumatol 2010 [Epub]. This study identifies pain-specific beliefs to be a specific area in which therapeutic intervention could benefit some children with juvenile idiopathic arthritis. 41 Walco GA, Dworkin RH, Krane EJ, et al. Neuropathic pain in children: special  considerations. Mayo Clin Proc 2010; 85:S33–S41. Extensive review of management options for some of the most difficult pain problems in CAYP. 42 Sherry DD, Wallace CA, Kelley C, et al. Short- and long-term outcomes of children with complex regional pain syndrome type I treated with exercise therapy. Clin J Pain 1999; 15:218–223.

31 Thakkar K, Dorsey F, Gilger MA. Impact of endoscopy on management of  chronic abdominal pain in children. Dig Dis Sci 2010 [Epub]. This study provides evidence that endoscopy is a helpful investigation to aid the management of FGID in CAYP.

43 Agrawal SK, Rittey CD, Harrower NA, et al. Movement disorders associated  with complex regional pain syndrome in children. Dev Med Child Neurol 2009; 51:557–562. Only study to highlight the frequency of movement disorders in CAYP with CRPS.

32 Heurtas-Ceballos AA, Logan S, Bennett C, Macarthur C. Dietary interventions for recurrent abdominal pain (RAP) and irritable bowel syndrome (IBS) in childhood (Review). The Cochrane Library 2009.

44 Saps M, Youssef N, Miranda A, et al. Multicenter, randomized, placebo controlled trial of amitriptyline in children with functional gastrointestinal disorders. Gastroenterology 2009; 137:1261–1269. This study finds no difference between active drug and placebo in children with FGID. Nonetheless, amitriptyline is shown to be well tolerated and efficacious.

33 Francavilla R, Miniello V, Magista AM, et al. A randomized controlled trial of  lactobacillus GG in children with functional abdominal pain. Pediatrics 2010 [Epub]. Further evidence that probiotics may have a role in the management of some cases of FGID in children. 34 Scarpellini E, Giorgio V, Gabrielli M, et al. Prevalence of small intestinal bacterial overgrowth in children with irritable bowel syndrome: a case–control study. J Pediatr 2009; 155:416–420.

45 Berenson F, Vasconcellos E, Pakalnis A, et al. Long-term, open-label safety study of oral almotriptan 12.5 mg for the acute treatment of migraine in adolescents. Headache 2010; 50:795–807. 46 Davies EH, Ollivier CM, Saint Raymond A. Paediatric investigation plans for  pain: painfully slow! Eur J Clin Pharmacol 2010; 66:1091–1097. A call to many parties to collaborate in clinical trials of analgesic agents in children.

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